Influence of sex on risk of bleeding in anticoagulated patients: a systematic review and meta-analysis

BackgroundThe risk of bleeding on anticoagulation varies between patients. It is uncertain whether sex influences this risk. ObjectivesTo determine if the risk of major bleeding differs between men and women receiving anticoagulation for atrial fibrillation or venous thromboembolism (VTE). MethodsWe searched MEDLINE, EMBASE, and Cochrane databases, and relevant conference proceedings, until February 2013. We included randomized controlled trials and prospective cohort studies of patients on therapeutic anticoagulation for atrial fibrillation or VTE. Two reviewers independently extracted data. The relative risk of bleeding in men compared to women was pooled using a random-effects model. ResultsForty-two studies including 94293 patients were eligible; 78044 patients (83%) had atrial fibrillation; 16156 patients (17%) had VTE; 37250 patients were women (40%); and there were 4147 major bleeds. The relative risk of major bleeding for men vs. women was 1.02 (95% CI 0.95-1.10; P=0.27 for heterogeniety). The relative risk was 1.02 (95% CI 0.95-1.09) in patients with atrial fibrillation and 0.80 (95% CI 0.65-0.98) in patients with VTE (P=0.03 for subgroup effect). Type of anticoagulant, intensity of anticoagulation, and whether patients began or were already established on anticoagulants at enrollment did not influence the relative risk of major bleeding in men compared to women. ConclusionsThe risk of major bleeding on anticoagulation appears to be the same in men and women, particularly if patients have atrial fibrillation. This finding is less certain for patients with VTE, in whom the risk of bleeding may be marginally lower in men compared to in women.